Glycosaminoglycans role in hippocampal neural networks interneuronal communications

Abstract

In the development of neurotechnologies, the search for applications for invasive neuroelectronic devices is relevant. One of the promising areas can be the development of ways of influencing intercellular communication, that is, not by acting on pre-, post- and extrasynaptic receptors, but on the extracellular matrix surrounding neurons and glia. For the development of bioelectronic pharmaceuticals, it is important to search for stimulation parameters at which a controlled change in the structural and functional parameters of the nervous tissue is possible. We considered one of the actual mechanisms of the molecular pathogenesis of SARS-CoV-2 infection - the induction of glycosaminoglycan metabolism. It is assumed that, getting into the olfactory epithelium and the olfactory bulbs of the brain, the virus is able to reach the structures of the central nervous system. When modeling changes in the enzymatic activity of hyaluronidase (0.1; 1.0; 10.0 U/ml) for 5 minutes in one of the key structures of the limbic system - the hippocampus (3-4-week-old ratpups, n = 64), the conditions for the transformation of intercellular contacts were revealed and evoked electrical activity of populations of CA1 region. The recorded development of synaptic plasticity processes has an adaptive potential at hyaluronidase concentrations not exceeding 1.0 U/ml.The in vitro method proposed in this work and a reasonable target for exposure - elements of the extracellular matrix, make it possible to simulate one of the mechanisms of the development of viral infection, optimize the process of preliminary screening of new medicinal substances that can minimize the risk of developing neuroinflammatory processes, and also substantiate the conditions for safe and/or therapeutic effects and electrical impulses on the elements of the nervous tissue.